CN104161760A - Compound anesthetic for racoon dogs as well as preparation method and application thereof - Google Patents
Compound anesthetic for racoon dogs as well as preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a compound anesthetic for racoon dogs as well as a preparation method and application thereof, and belongs to the fields of preparation and application of compound anesthetics for racoon dogs. The compound anesthetic for the racoon dogs comprises the following components: dexmedetomidine, midazolam and water for injection. The invention further discloses a method for preparing the compound anesthetic for the racoon dogs, and the method comprises the following steps: (1) mixing the dexmedetomidine and the midazolam; (2) adding the water for injection and mixing evenly to obtain the compound anesthetic for the racoon dogs. Animal experiments prove that the compound anesthetic for the racoon dogs has an excellent anesthetic effect on the racoon dogs, and is quick and steady in induction and waking, and excellent and balanced in calming, pain easing and muscle relaxation effects; the compound anesthetic has a marginal effect on the circulatory system, the respiratory system, blood indexes and partial liver and kidney indexes, and can be applied to preparing the clinical anesthetics for the racoon dogs.
Description
Technical field
The present invention relates to compound anesthetic, relate in particular to a kind of Nyctereutes procyonoides compound anesthetic, the invention still further relates to this Nyctereutes procyonoides by the preparation method of compound anesthetic and in the purposes of preparation Nyctereutes procyonoides in anaesthetic, belong to preparation and the applied technical field of compound anesthetic for Nyctereutes procyonoides.
Background technology
Nyctereutes procyonoides is a kind of small-sized Canis animals, and its another name has recoon dog, leopard cat etc., is mainly distributed in the countries such as the former Soviet Union, China, Mongolia, Japan, Korea, Finland and Denmark.Along with the rise of extraordinary Fur Animal Feeding, the cultivation of Nyctereutes procyonoides becomes the main flow kind in Fur Animal Feeding industry, and its aquaculture cost is low, and method for breeding is simple, and fur utilization rate is high.
In recent years, the research of combined anesthesia and application have become the main flow of anesthesia field development.Combined anesthesia is that multiple anesthetics and anesthesia are carried out to best of breed, thereby reduce dosage and the toxic and side effects of every kind of medicine, avoided using single medicine because consumption is excessive and arrive and deeply anaesthetize the unfavorable factor of bringing, to organism physiology moving obstacle minimum in the situation that, provide best anaesthesia technology.Foreign recommended has for the anesthetics of Canis animals: the compound xylazine of ketamine, the compound promazine of ketamine, dexmedetomidine Ketamine and apply separately free from worries etc.
Canis animals is of a great variety, and different animals is different to the sensitivity of same anesthetics and toleration.So, answer the characteristic of bound drug, various Canis animals physiological characteristics, body constitution etc. to select suitable anaesthetic kind and dosage.
The anesthesia of Nyctereutes procyonoides at present is nearly all used or deer anesthetis with dog, and these are not to develop for the physiological property of Nyctereutes procyonoides, easily occur in use anesthetic accident, cause certain economic loss.Therefore, urgently develop a kind of compound anesthetic that is applicable to Nyctereutes procyonoides of the development of the physiological property for Nyctereutes procyonoides.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of Nyctereutes procyonoides compound anesthetic of the development of the physiological property for Nyctereutes procyonoides, and this compound anesthetic is good to Nyctereutes procyonoides anaesthetic effect, and induction is quick, steady with recovery time, and anesthesia duration is long.
For solving the problems of the technologies described above, the technical solution used in the present invention is:
First the present invention provides a kind of Nyctereutes procyonoides compound anesthetic, comprising: Dexmedetomidine, midazolam and water for injection.
Described Nyctereutes procyonoides compound anesthetic, in every milliliter of compound anesthetic, the consumption of Dexmedetomidine is 0.4-0.5mg, the consumption of midazolam is 4-5mg;
Preferably, in every milliliter of compound anesthetic, the consumption of Dexmedetomidine is 0.5mg, and the consumption of midazolam is 4-4.5mg;
Most preferred, in every milliliter of compound anesthetic, the consumption of Dexmedetomidine is 0.5mg, and the consumption of midazolam is 4.5mg.
Dexmedetomidine (Dexmedetomidine Hydrochloride, DEX) is a kind of novel α
2-adrenoceptor high selectivity agonist, it can be optionally and α
1, α
2the ratio of epinephrine combination is 1600:1, with α
2the affinity of AR is 8 times of clonidine.Dexmedetomidine has good analgesia and sedation effect.
Midazolam (having another name called Midazolam) is water solublity Benzodiazepines tranquilizer, and its effect is relevant in conjunction with number with the acceptor site in GABA receptor complex, when combination rate reaches 25%-30%, has angst resistance effect; When combination rate reaches 25%-50%, there is sedation; When combination rate reaches 90%-100%, have syngignoscism, this effect is dose dependent, and the drug effect of midazolam is not only relevant with dosage, also closely related with pharmacokinetics feature.Midazolam can reduce the stress of animal effectively, because it has strong sedation, and anxiety and Amnesia; And can also obviously reduce the consumption of other anesthetics; When with other drug combined anesthesia animal, slight because of its impact on circulatory function, therefore, be specially adapted to the anesthesia of critical and shock animals.
The present invention is Dexmedetomidine+midazolam, ketamine+midazolam, and ketamine+Dexmedetomidine, Dexmedetomidine+acepromazine, xylazine+midazolam combination of two, anaesthetizes respectively Nyctereutes procyonoides, observes analgesia, calmness and flesh pine effect.Result shows, the combination analgesic effect of Dexmedetomidine+midazolam is significantly better than other combinations (P<0.05), and good analgesia time continues to grow (50min), calm best, flesh pine effect score is high compared with other four groups, at part-time point, compare significant difference (P<0.05) with other groups.Comprehensive analgesia, calmness and flesh pine effect draw, the combination of Dexmedetomidine+midazolam is better than other combination.The present invention filters out dexmedetomidine and midazolam optimum dosage by prescription consumption screening experiment, and the consumption of dexmedetomidine is preferably 0.05mg/kg, and the dosage of midazolam is preferably 0.40-0.45mg/kg, most preferably is 0.45mg/kg.
Nyctereutes procyonoides anesthesia test confirms, Nyctereutes procyonoides compound anesthetic of the present invention, and calmness, analgesia and flesh pine are respond well.May be due to the effect of DEX, DEX has good analgesia, calmness and the effect of flesh pine, and it can act on presynaptic membrane and the relay cell postsynaptic membrane of posterior horn of spinal cord, causes cell hyperpolarization, stops pain signal up to brain transmission; Also may DEX directly and brain stem nucleus ceruleus α
2receptors bind, thus analgesic activity is played in the conduction of termination pain signal; The sedation effect of midazolam is good, with the compound sedation effect of more having strengthened of Dexmedetomidine.
The present invention also provides a kind of method of compound anesthetic for described Nyctereutes procyonoides of preparing, and comprises the following steps: Dexmedetomidine and midazolam are mixed; Add water for injection, mix homogeneously, obtains.
Be preferably, under 20 ℃ of aseptic conditions, accurately weigh Dexmedetomidine and midazolam, by it mixing, put into an ampulla that sterilizing seal is good, then add sterilized water for injection mix homogeneously, and be placed on vortex agitator (50HZ, 25w, 1500rpm) upper concussion 20s, shakes 10 times altogether, until macroscopy is advisable without dissolved powders not.
10min before anesthesia, take 0.25ml/kg subcutaneous injection concentration as 0.2mg/ml atropine sulfate injection; Then, then inject Nyctereutes procyonoides compound anesthetic of the present invention, its consumption is 0.1ml/kg.
The present invention also provides described Nyctereutes procyonoides preparing the purposes in anaesthetic for Nyctereutes procyonoides with compound anesthetic.
The present invention be take Nyctereutes procyonoides as laboratory animal, by of the present invention for Nyctereutes procyonoides compound anesthetic (Y group) and clinical conventional four kinds of compound anesthetic dogs sleep precious (Q group), free from worries 50 (Z groups), speed sleep new II (SX group) and relaxing sleep rather (SN group) carry out Comparison.
Experimental result shows: (1) Y group anaesthetic effect is best, and analgesia, calmness and flesh pine are respond well, balanced; (2) to blood circulation, monitoring shows, five groups of body temperature all have decline in various degree, and wherein Y group declines at most, is 2.1 ℃; Between group, to compare difference all not remarkable for each time point; Five groups of hearts rate all have in various degree and raise after anesthesia, slow decreasing subsequently, and Q group and SX group are not remarkable in each time point difference, and SN organizes and Y group significant difference (P<0.05) in 40-50min; Five groups of blood pressures be also first rise after downward trend, wherein Y group systolic pressure is except 0min-5min, between all the other each time points, domain of walker is little, difference not significantly (P>0.05) whole; Y group is after 10min, and DBP amplitude of variation is little, is down to minimum when 60min; (3) respiratory monitoring is shown, Y group detecting sphygmus and blood oxygen saturation institute is influenced the slightest, remain at more than 95%, and excursion is little in whole observation process; Y group is to breathing last CO
2concentration affects is the slightest, Q group and all the other four groups of comparing differences remarkable (P<0.05); Y group RR changes little at each time point, difference is remarkable (P>0.05) not; (4) electrocardiogram monitoring is shown, Y group is slight to each waveform persistent period and each wave band voltage influence.(5) physiochemical indice and some biochemical assay show, five groups all slight on erythrocyte, leukocyte, hemoglobin, liver and renal function impact, body do not produced to detrimental effect.
Enter after anesthetic stage, Z group induction time is the shortest is 2.24 ± 1.06min, the longest 7.58 ± 1.52min of SX group induction time, and Y group induction time 5.68 ± 1.23min is close with Q group; Y group is compared significant difference (P<0.05) with Z group, SN group; Five groups of Induction Process are all more steady, the rare struggle phenomenon of Nyctereutes procyonoides.From anesthesia duration, SX holds time the longest, and Q group and Y group are taken second place, but all can continue more than 1 hour, difference is significantly (P>0.05) not, can be for some as sterillization, little bone surgery etc., and Z group and SN group all can only maintain about 40min.Combination analgesia again from Y group is held time, calm, the loose several indexs of flesh, can be to find out the surgical operation that can do simple and even medium complexity under its narcotism.From recovery time, Y group shortest time, only there is 10.26 ± 5.38min, this index can compare favourably with inhalation anesthesia completely, and the process of reviving is also very steady, quiet,, there is not whining and blindly rocking walking phenomenon in the state disappearing again after there will not be righting reflex for the first time to recover yet.
Composite score, Nyctereutes procyonoides of the present invention is best to Nyctereutes procyonoides anaesthetic effect with compound anesthetic, and calmness, analgesia and flesh pine are respond well, balanced; The induction of anesthesia time is 5.68 ± 1.23min, and anesthesia duration is 65.23 ± 4.37min, and recovery time is 10.26 ± 5.38min; Slight to blood circulation, respiratory system, physiochemical indice and part Liver and kidney Index Influence, can be used for preparing Nyctereutes procyonoides anaesthetic.
The specific embodiment
Below in conjunction with specific embodiment, further describe the present invention, advantage and disadvantage of the present invention will be more clear along with description.It should be understood that described embodiment is only exemplary, does not form any restriction to scope of the present invention.It will be understood by those skilled in the art that lower without departing from the spirit and scope of the present invention and can the details of technical solution of the present invention and form be modified or be replaced, but these modifications or replacement all fall into protection scope of the present invention.
The preparation of compound anesthetic for embodiment 1 Nyctereutes procyonoides
Under 20 ℃ of aseptic conditions, accurately weigh Dexmedetomidine 4mg and midazolam 40mg, by it mixing, put into a 20ml ampulla that sterilizing seal is good, add again 10ml sterilized water for injection mix homogeneously, and be placed on vortex agitator (50HZ, 25w, 1500rpm) upper concussion 20s, shake altogether 10 times, until macroscopy is without dissolved powders not, obtain.
The preparation of compound anesthetic for embodiment 2 Nyctereutes procyonoidess
Under 20 ℃ of aseptic conditions, accurately weigh Dexmedetomidine 5mg and midazolam 50mg, by it mixing, put into a 20ml ampulla that sterilizing seal is good, add again 10ml sterilized water for injection mix homogeneously, and be placed on vortex agitator (50HZ, 25w, 1500rpm) upper concussion 20s, shake altogether 10 times, until macroscopy is without dissolved powders not, obtain.
The preparation of compound anesthetic for embodiment 3 Nyctereutes procyonoidess
Under 20 ℃ of aseptic conditions, accurately weigh Dexmedetomidine 5mg and midazolam 40mg, by it mixing, put into a 20ml ampulla that sterilizing seal is good, add again 10ml sterilized water for injection mix homogeneously, and be placed on vortex agitator (50HZ, 25w, 1500rpm) upper concussion 20s, shake altogether 10 times, until macroscopy is without dissolved powders not, obtain.
The preparation of compound anesthetic for embodiment 4 Nyctereutes procyonoidess
Under 20 ℃ of aseptic conditions, accurately weigh Dexmedetomidine 5mg and midazolam 45mg, by it mixing, put into a 20ml ampulla that sterilizing seal is good, add again 10ml sterilized water for injection mix homogeneously, and be placed on vortex agitator (50HZ, 25w, 1500rpm) upper concussion 20s, shake altogether 10 times, until macroscopy is without dissolved powders not, obtain.
The component screening experiment of experimental example 1 compound anesthetic
1, experimental technique
By different pharmaceutical combination, be specially Dexmedetomidine+midazolam, ketamine+midazolam, ketamine+Dexmedetomidine, Dexmedetomidine+acepromazine, xylazine+midazolam; Group Chinese medicine dosage is respectively Dexmedetomidine 40 μ g/kg, midazolam 0.5mg/kg, ketamine 8mg/kg, acepromazine 0.02mg/kg, xylazine 1mg/kg.
Every group of medicine be anaesthesia experiment animal Nyctereutes procyonoides respectively, and 5 every group, observe analgesia, calmness and flesh pine effect, the table 1 of take is marked as standard.
Table 1 anesthesia standards of grading
2, experimental result
Experimental result shows (table 2-4), various medicines are combined, wherein the combination analgesic effect of Dexmedetomidine+midazolam is significantly better than other combinations (P<0.05), and good analgesia time continues to grow (50min); The calm best combination (P<0.05) that is significantly better than Dexmedetomidine+acepromazine and xylazine+midazolam of the combination of Dexmedetomidine+midazolam aspect calm, the good calm time reaches (60min), and after anesthesia, 10～50min time period sedation effect reaches full marks; Combination flesh pine effect score at the Dexmedetomidine+midazolam of anestheticing period is high compared with other four groups, and in 10min-50min, each time point is all full marks, compares significant difference (P<0.05) at part-time point with other groups.
Comprehensive analgesia, calmness and flesh pine effect can draw, the combination of Dexmedetomidine+midazolam is obviously better than other combination.
The comparison of table 2 prescription research-different pharmaceutical combination analgesic effect
Note: same column comparison, shoulder mark capitalization identical table differential different not remarkable (P>0.05), the female different significant differences (P<0.05) that represent of shoulder marking-up; Relatively, shoulder is marked lower case identical table differential different not remarkable (P>0.05) to colleague, the female different expression significant differences (P<0.05) of shoulder marking-up.
The comparison of table 3 prescription research-different pharmaceutical combination sedation effect
Note: statistical analysis labelling is with table 2.
The comparison of table 4 prescription research-different pharmaceutical combination flesh pine effect
Note: statistical analysis labelling is with table 2.
The prescription consumption screening experiment of experimental example 2 compound anesthetics
On experimental example 1 basis, dexmedetomidine, midazolam are measured to the anaesthetic effect of various combinations by two factor three levels (table 5), concrete outcome is in Table 6.
Table 5 factor level table
Table 6 component dosage determine that (after two kinds of medicine composite injections, 20min marks, n=5)
Note: data are relatively takeed on the different capitalizations of mark and represented significant difference (P < 0.05); The identical capitalization of shoulder mark represents difference not remarkable (P > 0.05).
Use the various combination subcutaneous injection Nyctereutes procyonoides being formed by dexmedetomidine and midazolam, observe the situations such as biological reflection, calmness, analgesia, flesh pine, the anesthetic action of various combination is comprehensively analyzed and evaluated, the consumption that Preliminary screening goes out dexmedetomidine is preferably 0.05mg/kg, the dosage of midazolam is preferably 0.40-0.45mg/kg, most preferably is 0.45mg/kg.
Experimental example 3 Nyctereutes procyonoides of the present invention uses compound anesthetic and other four kinds of compound anesthetics to Nyctereutes procyonoides Anesthetic Effect
1, laboratory animal and reagent
25 of the healthy recoon dogs in Nyctereutes procyonoides field, purchased from red flag township Zhao Panqinghu Nyctereutes procyonoides plant, body weight 7.83 ± 0.42kg, the age 9-10 monthly age, be the qualified healthy animal of quarantine, every physical signs is normal, and mental status is good.Experimental animal is all raised in equivalent environment, unified feeding.Fasting 12h before test, more than prohibiting water 5h.
Dog dormancy precious (purchased from Qingdao Hanhe Animal and Plant Medicine Co., Ltd, lot number 2012022701); A kind of Canis animals specific complex anesthetis of surgery teaching and research room of Quan Mianbaoshi Northeast Agricultural University development,, piperazine sharp pyridine peaceful by xylidinothiazoline, strong pain, ketamine form (by single injection volume calculating in mixture) according to 2.5:0.12:0.5:0.25.
Free from worries 50; Free from worries is the combined anesthesia medicine that French Virbac produces, and has free from worries 20 (20mg/ml), free from worries 50 (50mg/ml) and free from worries 100 (100mg/ml) 3 kinds of concentration.Main component is tiletamine and zolazepam, by 1:1, is mixed.
Speed dormancy new II (purchased from Changchun military supplies university veterinary institute); It is newly a kind of combined anesthesia preparation that speed is slept, and claims again 846 mixture, by the general anesthetic of Changchun military supplies university veterinary institute development, is the compound preparation of rather being made by hydrochloric acid dihydroetorphine (DHM99), haloperidol, Baoding; Every milliliter of speed is slept and is newly contained the peaceful 60mg in Baoding, hydrochloric acid dihydroetorphine 4 μ g, haloperidol 2.5mg.
Dormancy injection for curing (purchased from Agricultural University Of Nanjing's toy disease research chamber, lot number 20130701) relaxes; The dormancy injection for curing that relaxes is 2011 Nian You Agricultural University Of Nanjing toy disease research chamber developments, a kind of novel toy combined anesthesia preparation being formed by ketamine, xylazine and three kinds of medicament mixed of midazolam; Ketamine (8g/100ml), xylazine (0.9g/100ml) and midazolam (0.2g/100ml).
Atropine sulfate injection (purchased from Jilin Province Hua Mu animal health-care product company limited, lot number 130506);
The former powder of Dexmedetomidine (purchased from Shenzhen Da Aisen Science and Technology Ltd., lot number 130718);
The former powder of midazolam (purchased from Shi Feng bio tech ltd, Shanghai, lot number 131104);
Glutamic oxaloacetic transaminase, GOT testing cassete (builds up Bioengineering Research Institute purchased from Nanjing, lot number: 20131129);
Glutamate pyruvate transaminase testing cassete (builds up Bioengineering Research Institute purchased from Nanjing, lot number: 20131130);
Alkali phosphatase testing cassete (builds up Bioengineering Research Institute purchased from Nanjing, lot number: 20131127);
Blood urea nitrogen testing cassete (builds up Bioengineering Research Institute purchased from Nanjing, lot number: 20131129);
Creatinine testing cassete (builds up Bioengineering Research Institute purchased from Nanjing, lot number: 20131128);
Dexamethasone sodium phosphate injection (purchased from Zhengzhou Zhuo Feng pharmaceutical Co. Ltd, lot number 137043C).
2, experimental technique
2.1 animal grouping and anesthesia
Using the healthy Nyctereutes procyonoides in 25 of Nyctereutes procyonoides fields as laboratory animal, be divided at random 5 groups, 5 every group; One group (Q group) sleeps precious with 0.2ml/kg dosage intramuscular injection dog; Two groups (Z groups) are with 0.15ml/kg dosage intramuscular injection free from worries 50; Three groups (SX group) is with the new II of 0.1ml/kg dosage intramuscular injection speed dormancy; Four groups (SN group) relaxed and rather slept with the intravenous injection of 0.1ml/kg dosage; Five groups (Y group) is with the Nyctereutes procyonoides compound anesthetic of the 0.1ml/kg dosage intramuscular injection embodiment of the present invention 4 preparations.
Anesthesia: 10min before anesthesia, take 0.25ml/kg subcutaneous injection concentration as 0.2mg/ml atropine sulfate injection; Inject respectively corresponding preparation for callouse for five groups subsequently.When appearring in Nyctereutes procyonoides, righting reflex loss is designated as the anesthesia time started (0min).
2.2 monitoring index
(1) the anaesthesia process physiology monitoring Monitoring Indexes time: before anesthesia, enter after anesthetic stage 0,5,10,20,30,40,50 and 60min.
1) general Monitoring Indexes
Body temperature (T): measure with Philips breath cycle monitor probe for detecting temperature loading test animal internal rectum;
Heart rate (HR): monitor at sublingual vein with Philips breath cycle monitor probe clip;
Analgesia, calm, flesh is loose: the table 1 of take is marked as standard, at each time point, respectively every test is monitored;
Induction time: just disappear to laboratory animal righting reflex from injecting anesthetic preparation, use stopwatch writing time;
Anesthesia duration: just disappear and recover to righting reflex from righting reflex, use stopwatch writing time;
Recovery time: return to and can walk on their own from righting reflex, use stopwatch writing time.
2) respiratory system Monitoring Indexes
After Nyctereutes procyonoides anesthesia, carry out tracheal intubation, then device is connected to PL3516B49 and leads physiological monitor more.
Monitoring index is: respiratory frequency (RR), breathe last CO
2concentration (PetCO
2), minute ventilation volume (MV), tidal volume (TV).
3) blood circulation Monitoring Indexes
Detecting sphygmus and blood oxygen saturation (SpO
2): Datex respiratory monitor sensor probe is clipped on experimental animal tongue and is monitored.
Non-invasive blood pressure: Datex respiratory monitor oversleeve is enclosed within to experimental animal forelimb elbow joint place and monitors, comprising: systolic pressure (SBP), diastolic pressure (DBP) and mean arterial pressure (MAP).
4) electrocardiogram monitoring
Operational approach: PL3516B49 is led to sensing syringe needle on NEG on physiological monitor, EARTH and tri-electrodes of POS more, and to insert respectively right fore, right hind and left hind subcutaneous, carries out monitor ECG.Notice that each on line can not intersect.
(2) routine blood test detects
Blood sampling time point: before anesthesia, enter after anesthetic stage 0,1,2,4h.
Operational approach: take a small amount of blood sample with blood taking needle respectively at above time point, detect with auspicious BC-2600Vet advanced in years fully automatic blood cytoanalyze for animals, and print result.
(3) liver function, kidney merit detect
Blood sampling time point: before anesthesia, enter after anesthetic stage 0,1,2,4,8,12,24,48,72h.
Operational approach: at above time point, with vacuum test tube, take blood sample 3ml respectively, with low speed autobalancing centrifuge with 3000r/min by the centrifugal 10min of blood sample.Get upper serum, put into refrigerator-20 ℃ layer, standby.
Liver function, kidney merit detection method: the operation to specifications respectively of glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, GOT, alkali phosphatase, creatinine, five kinds of test kits of blood urea nitrogen, detects each sample with TU-1810 ultraviolet-uisible spectrophotometer, and records each result.
2.3 data statistical approach
Data result mean+SD
represent, adopt SPSS18.0 to carry out data analysis arrangement.P < 0.05 is significant difference, and P<0.01 is that difference is extremely remarkable.
3, experimental result
3.1 anesthesia scorings
3.1.1 analgesia scoring
Experimental result shows and to enter (table 7) after anesthetic stage, and each time point of 0min-60min Q group, Z group, SX group are similar with SX score, comparing difference not significantly (P>0.05) between group; Y group is high compared with other four groups in each time point score of 0min-60min, and in 10min-50min, each time point is all full marks, and same time point is compared with other groups, significant difference (P<0.05).
Table 7 analgesia appraisal result
Note: relatively, shoulder is marked capitalization identical table differential different not remarkable (P>0.05) to colleague, the female different expression significant differences (P<0.05) of shoulder marking-up; Same column comparison, shoulder mark lower case identical table differential different not remarkable (P>0.05), the female different significant differences (P<0.05) that represent of shoulder marking-up.
---represent countless certificates.
3.1.2 calm scoring
Experimental result shows (table 8), enters after narcotism, and between group, relatively, Y group there are differences significantly (P<0.05) at 0～10min and other each groups, and this good calm time remaining of Y group is the longest, until monitoring finishes.In group, relatively, only have Y group sedation effect during monitoring to stablize the most (P>0.05).
The calm appraisal result of table 8 anesthesia
Note: statistical analysis labelling is with table 7.
3.1.3 flesh pine scoring
Experimental result demonstration (table 9), enters after narcotism, and Q group is better than other groups with Y group flesh pine state, and similar in each time point score, comparing difference is remarkable (P>0.05) not; But Q organizes the good flesh pine time and is only maintained to 40min, is shorter than Y group.
Table 9 anesthesia flesh pine appraisal result
Note: statistical analysis labelling is with table 7.
3.2 anesthesia duration monitoring results
Experimental result shows (table 10), enters after anesthetic stage, and SX group induction time is the longest, compares significant difference (P<0.05) with Z group with SN group, and Z group induction time is the shortest; It is the longest that SX organizes anesthesia duration, and Q group and Y organize anesthesia duration and be more or less the same, and difference is remarkable (P>0.05) not, and Z group and SN group comparing difference be remarkable (P>0.05) not; Recovery time Y group is the shortest, and Y group, SN group and SX group are compared, and recovery time difference is remarkable (P>0.05) not.
Table 10 anesthesia duration monitoring result (min,
n=5)
Note: relatively, shoulder is marked capitalization identical table differential different not remarkable (P>0.05) to colleague, the female different expression significant differences (P<0.05) of shoulder marking-up.
3.3 anaesthetic effect comprehensive monitoring results
3.3.1 anesthetic stage routine clinical Monitoring Indexes
3.3.1.1 temperature monitoring
Experimental result shows (table 11), and each group enters after narcotism, along with anesthesia duration extends, body temperature is totally on a declining curve, and wherein Q group, Z group and Y group temperature decline are obvious, when anesthesia finishes, decline respectively 1.74 ℃, 1.13 ℃ and 2.1 ℃, Q group is when 50min-60min, with basic value comparison, significant difference (P<0.05), Z group is when 30min-60min, with basic value comparison, significant difference, Y group is at 30min-60min and basic value comparison, significant difference; SX group body temperature when 10min slightly raises, and declines subsequently.SN group temperature decline is slow, and amplitude of variation is little, during 30min-60min and basic value comparison, and significant difference (P<0.05).Between group, each time point compares, and difference is not significantly (P>0.05) all.
Table 11 temperature monitoring result (℃,
n=5)
Note: * is expressed as different time points and basic value comparison in group, and P<0.05 is significant difference;
Between organizing relatively, shoulder marking-up parent phase is with representing difference not significantly (P>0.05), the female different significant differences (P<0.05) that represent of shoulder marking-up for five groups of same time points;
---represent countless certificates.
3.3.1.2 breathing rate monitoring
Experimental result shows (table 12), enters after anesthetic stage, and Q group, Z group and SX group are when 0min, RR obviously raises, with basic value comparison, difference is remarkable (P>0.05) not, and each group surpasses respectively 15%, 11% and 20% of basic value.Subsequently, from anesthesia 10min, Respiration Rate declines obviously, with basic value comparison, and significant difference (P<0.05).SN group 0min-10min after anesthesia, RR declines clearly, during from 20min, slowly raises.Y group RR changes little at each time point, difference is remarkable (P>0.05) not.Y group compares with SN group, at 50min-60min significant difference (P<0.05).
Table 12 breathing rate monitoring result (beat/min,
n=5)
Note: statistical analysis labelling is with table 11.
3.3.1.3 rhythm of the heart
Experimental result shows (table 13), each group is after entering narcotism, five groups of HR all raise when 0min, with basic value comparison, raise respectively 37%, 72%, 12%, 19% and 15%, only have Q group, Z group and SN group significant difference (P<0.05), Q group and SX group HR from 5min are on a declining curve, and Z group and SN group start HR rising from 50min and 30min respectively; Z group compares at each time point and other groups, significant difference (P<0.05), and Q group and SX group are not remarkable in each time point difference, SN group and Y group significant difference (P<0.05) in 40-50min.
Table 13 rhythm of the heart result (beat/min,
n=5)
Note: statistical analysis labelling is with table 11.
3.3.1.4 detecting sphygmus and blood oxygen saturation monitoring result
Experimental result shows (table 14), enters after anesthetic stage five groups of SpO
2all can remain on more than 85%, Y organizes SpO
2suffered impact is the slightest, substantially can remain on more than 95%, and excursion is little.SX group is continuous decrease trend in 20min-60min.SN group is when 5min, and with 0min comparing difference remarkable (P<0.05), other times excursion is little, within the scope of Nyctereutes procyonoides normal physiological; SN group compares with Y group, in 5min-30min, and significant difference (P<0.05).In each time point variation of anesthesia greatly, but all within the scope of normal physiological, there is not significant difference (P>0.05) in Q group and Z group.
Table 14 blood oxygen saturation (SpO
2) monitoring result (%,
n=5)
Note: relatively, shoulder is marked capitalization identical table differential different not remarkable (P>0.05) to colleague, the female different expression significant differences (P<0.05) of shoulder marking-up; Same column comparison, shoulder mark lower case identical table differential different not remarkable (P>0.05), the female different significant differences (P<0.05) that represent of shoulder marking-up.
3.3.2 respiratory system Monitoring Indexes
3.3.2.1 breathe last CO
2concentration monitor result
Experimental result shows (table 15), and Nyctereutes procyonoides enters after narcotism, and Z group and Y group are all on a declining curve in whole anaesthesia process, and Y group is to breathing last CO
2concentration affects is the slightest, and between each time point, domain of walker is little, no difference of science of statistics (P>0.05).Q group, SX group and SN group have Flare-up when 5min, 18.5mmHg, 3.2mmHg and 19.15mmHg have raise respectively, Q group is at each time point significant difference (P<0.05) of 5min-60min, SN group is at each time point significant difference (P<0.05) of 5min-20min, on a declining curve subsequently; Q group and all the other four groups of comparing differences are (P<0.05) significantly, and Z group, SX group and SN group are at each time point comparing difference not significantly (P>0.05).
Table 15 is breathed last CO
2concentration monitor result (mmHg,
n=5)
Note: statistical analysis labelling is with table 14.
3.3.2.2 minute ventilation volume monitoring result
Experimental result shows (table 16), and MV in several groups is the highest for Y group, and this illustrates that this group is the slightest on the impact of ventilation per minute, and Y group is down to minimum (P<0.05) when 30min, slowly raises again subsequently.Z group MV slowly raises, each time point significant difference (P<0.05) in 10min-40min.Q group and SN group MV are on a declining curve in the anesthesia starting stage, drop to respectively 1.24L/min and 2.25L/min, slowly raise subsequently, and during to 40min, MV is the highest, and two groups at each time point difference all remarkable (P<0.05).SX group is on a declining curve in whole anaesthesia process, is down to minimumly during to 50min, is 1.2L/min.
Table 16 minute ventilation volume monitoring result (L/min,
n=5)
Note: statistical analysis labelling is with table 14.
3.3.2.3 tidal volume monitoring result
Experimental result shows (table 17), and Q group and Y group TV reduce gradually after anesthesia, are down to minimum 192.28ml and 183.71ml respectively when 40min and 30min, start subsequently to raise gradually.Z group and SN group are at the anesthesia initial stage, and TV first declines, during to 40min, raise again, and only SN group each time point and 5min comparison in 30min-40min, significant difference (P<0.05).SX group TV is first Flare-up when 10min, slow decreasing subsequently, each time point and 5min comparison in 10min, 30min and 40min, significant difference (P<0.05).
Table 17 tidal volume monitoring result (ml,
n=5)
Note: statistical analysis labelling is with table 14.
3.3.3 blood circulation Monitoring Indexes
3.3.3.1 systolic pressure monitoring result
Experimental result shows (table 18), and Nyctereutes procyonoides enters after narcotism, and each group SBP in 0min-5min raises, on a declining curve subsequently; Wherein, Z group and SN group are when 40min-60min, and SBP has slow rise, and tends towards stability; Y group is except 0min-5min, and between all the other each time points, domain of walker is little, and difference is remarkable (P>0.05) not.Q group and SX group are compared, and each time point difference is not remarkable; In 0min-5min, Z group SBP raises the most obvious, is that 49.8%, Q group and the rising of Y group are less, is respectively 8.22% and 16.39%; In 10min-60min, Y group is organized each time point with Q group, SX and is compared, significant difference (P<0.05).
Table 18 systolic pressure (SBP) monitoring result (mmHg,
n=5)
Note: statistical analysis labelling is with table 11.
3.3.3.2 diastolic pressure monitoring result
Experimental result shows (table 19), and each group enters after narcotism, and in 0min-5min, DBP slightly raises, and wherein Z group raises the most obviously, is 40.7%, and subsequently, it is on a declining curve that each organizes DBP, but Z group and SN group be when 40min-60min, and DBP gos up to some extent; Y group is after 10min, and DBP amplitude of variation is little, is down to minimum when 60min.
Table 19 diastolic pressure (DBP) monitoring result (mmHg,
n=5)
Note: statistical analysis labelling is with table 11.
3.3.3.3 mean arterial pressure
Experimental result shows (table 20), each group enters after narcotism, in 0min-5min, MAP raises, slow decreasing subsequently, Q group is down to minimum when 40min, is 75.32mmHg, slowly raises again subsequently, anaesthetize each time point and basic value comparison, difference is remarkable (P>0.05) not; Z group and SN group decline at most when 30min, start subsequently to raise, and tend towards stability; SX group and Y group be anaesthetizing initial stage MAP raise respectively 21.37mmHg and 21.14mmHg, with basic value comparison, and significant difference (P<0.05), but all in Nyctereutes procyonoides physiological range, change.
Table 20 mean arterial pressure (MAP) monitoring result (mmHg,
n=5)
Note: statistical analysis labelling is with table 11.
3.3.4 electrocardiogram monitoring result
3.3.4.1P ripple, R ripple and T ripple monitoring result
Experimental result shows (table 21), five groups enter after narcotism, Q group, Z group and SN group P wave duration Flare-up when 20min, raise respectively 99.07%, 8.21% and 12.43%, slow decreasing subsequently, wherein each time point of Q group 20min-30min is compared with 10min, significant difference (P<0.05); SX group continues to raise in 10min-50min always, when 60min, declines; The Y group P wave duration slowly reduces at whole anesthetic stage, at each time point, does not have significant difference.
SX group and SN group R wave voltage, after anesthesia, are down to respectively minimumly at 30min and 20min, and compare respectively significant difference (P<0.05), subsequently rising with 10min separately; Q group R wave voltage continues to raise, and rises to the highlyest when 50min, is 2.88602mV, and in 30min-50min, each time point is compared with 10min, significant difference.Z group R wave voltage is irregular at anesthetic stage, when 30min, and significant difference; Y group is at whole anesthetic stage continuous decrease, but reduction amplitude is little, in each time period, does not have significant difference.
Q group and Z group T wave voltage after anesthesia, at 20min and 30min, be down to respectively minimum, slowly rising subsequently, wherein Q group each time point when 30min-50min is compared with 10min, significant difference (P<0.05); SX group, SN group and Y group T wave voltage first raise, and decline subsequently, and tend towards stability.
3.3.4.2P-R the monitoring result of section, Q-T section, S-T section and QRS ripple
Experimental result shows (table 22), enter after anesthetic stage, each is organized the P-R section persistent period and all raises, wherein Q group, SN group and Y group all rise to the highest when 30min, for 0.08380s, 0.04856s and 0.05605s, slow decreasing tending towards stability subsequently, each time point and 10min comparison, difference is not remarkable; Z organizes the P-R section persistent period, is Flare-up when 20min, is subsequently slow decreasing trend, and in whole anaesthesia process, fluctuation range is little; The SX group persistent period raises always, the 0.02987s that raises during to 60min, 60min and 10min comparison, significant difference (P<0.05).Between five groups, each time point compares, and does not have significant difference (P>0.05).
Q group and Y group Q-T section persistent period first raise reduces subsequently, wherein Q group each time point and 10min comparison in 30min-50min, significant difference (P<0.05), it is little that Y organizes each time point fluctuation range, there is not significant difference, but two groups of each time point comparisons in 30min-50min, significant difference (P<0.05); The SX group Q-T section persistent period changes greatly, each time point and 10min comparison in 40min-50min, significant difference (P<0.05); Z group and SN organize continuous decrease, all when 40min, are down to minimumly, are respectively 0.16720s and 0.05265s, and two groups when 10min, 30min and 40min, significant difference (P<0.05).
Q group S-T section voltage raises gradually at anesthetic stage, rises to the highlyest during to 50min, is 0.17218mV, Q group and the comparison when 10min, 20min and 60min of Y group, and significant difference, remarkable with SN group comparing difference when the 30min-40min; Y group S-T section voltage continues to raise, but rising amplitude is little, each time point and 10min comparison, and difference is not remarkable; Z group, SX group and SN group voltage first reduce, and are down to respectively minimumly when 20min, 40min and 20min, raise subsequently and tend towards stability.
After anesthesia, the first short time of Q group QRS wave duration declines, and slowly raises subsequently, and each time point difference is not remarkable; And the SN group QRS wave duration declines always, but reduction amplitude is little, all in 0.0044ms, fluctuates; SX group, Z group and Y group persistent period first raise, and reduce subsequently, and wherein only Z group, when 30min, is organized comparing differences significantly (P<0.05), the equal no difference of science of statistics of other times with other.
3.3.5 routine blood test monitoring result
Experimental result demonstration, if table 23 is to table 27, each group enters after anesthetic stage, and Z group and SN group WBC raise excessive when anesthesia, with Q group, SX and Y group, at part-time point significant difference (P<0.05).Each is organized RBC and is mostly the trend that first raises, and declines subsequently, and each time point does not exist significant difference.Z group PLT raises larger, exceeds Nyctereutes procyonoides normal physiological scope.Except Z group Gran quantity is for first declining, outside raising subsequently; All the other four groups are first rising, and downward trend subsequently; And Z group Lym number raises too much in 0min-4h, exceed Nyctereutes procyonoides normal physiological scope.
Table 23 Q group physiochemical indice monitoring result
Note: statistical analysis labelling is with table 11.
Table 24 Z group physiochemical indice monitoring result
Note: statistical analysis labelling is with table 11.
Table 25 SX group physiochemical indice monitoring result
Note: statistical analysis labelling is with table 11.
Table 26 SN group physiochemical indice monitoring result
Note: statistical analysis labelling is with table 11.
Table 27 Y group physiochemical indice monitoring result
Note: statistical analysis labelling is with table 11.
3.3.6 biomonioring result
Experimental result shows, if table 28 is to 32, enters after anesthetic stage, and each organizes ALT all rising in various degree, wherein Q group and Z group all when 24h and 48h, raise larger, with basic value comparing difference remarkable (P<0.05) separately; SN group rises to peak when 4h, remarkable with basic value comparing difference; Y group, in 2h-8h, raises more, compares significant difference (P<0.05) with other groups; SX group is at each time period no difference of science of statistics.
Five groups of AST are all the trend that first raises and reduce afterwards in anaesthesia process, but all within normal range, fluctuate, only SX group each time point and other group comparisons in 4h-12h, significant difference (P<0.05), other times point no difference of science of statistics.
Q group and SN organize ALP when anesthetic stage, present one and cross the trend raising after property reduces, and variation is subsequently comparatively stable, all not remarkable in each time point difference; Z group, SX group and Y group ALP first raise, reduce gradually subsequently, wherein only Z group 48h and SX group during at 8h with other group comparisons, significant difference (P<0.05), other each time point no difference of science of statistics.
Q group and Z organize BUN and in whole anaesthesia process, change more irregularly, but fluctuation range is little, all within normal range, wherein Q group in 12h-24h with basic value comparison, significant difference (P<0.05); SX group, SN group and Y group BUN are first and slowly raise, downward trend gradually subsequently, wherein SN group when 8h and basic value comparison, significant difference (P<0.05).SN group is each time point and other group comparisons in 12h-72h, significant difference (P<0.05).
SX group Crea has Flare-up when 0min, slow decreasing subsequently, but when 2h, decline too much, with basic value comparison, significant difference (P<0.05); Other groups Crea is first and raises, subsequently downward trend gradually.Wherein, Z group when 1h, 2h and 12h and other each group relatively, significant difference (P<0.05), SX group is each time point and other group comparing differences remarkable (P<0.05) in 1h, 4h and 12h-48h, Y group is each time point and other group comparisons in 0min-4h, significant difference (P<0.05), other times point no difference of science of statistics.
Table 28 Q group liver function and kidney merit testing result
Note: statistical analysis labelling is with table 11.
Table 29 Z group liver function and kidney merit testing result
Note: statistical analysis labelling is with table 11.
Table 30 SX group liver function and kidney merit testing result
Note: statistical analysis labelling is with table 11.
Table 31 SN group liver function and kidney merit testing result
Note: statistical analysis labelling is with table 11.
Table 32 Y group liver function and kidney merit testing result
Note: statistical analysis labelling is with table 11.
Claims (7)
1. a Nyctereutes procyonoides compound anesthetic, is characterized in that, comprising: Dexmedetomidine, midazolam and water for injection.
2. according to Nyctereutes procyonoides compound anesthetic claimed in claim 1, it is characterized in that: in every milliliter of compound anesthetic, the consumption of Dexmedetomidine is 0.4-0.5mg, the consumption of midazolam is 4-5mg.
3. according to Nyctereutes procyonoides compound anesthetic claimed in claim 2, it is characterized in that: in every milliliter of compound anesthetic, the consumption of Dexmedetomidine is 0.5mg, the consumption of midazolam is 4-4.5mg.
4. according to Nyctereutes procyonoides compound anesthetic claimed in claim 3, it is characterized in that: in every milliliter of compound anesthetic, the consumption of Dexmedetomidine is 0.5mg, the consumption of midazolam is 4.5mg.
5. prepare a method for compound anesthetic for Nyctereutes procyonoides described in claim 1,2,3 or 4, it is characterized in that, comprise the following steps: (1) mixes Dexmedetomidine and midazolam; (2) add water for injection, mix homogeneously, obtains.
6. in accordance with the method for claim 5, it is characterized in that: the described mixing of step (2) is 50HZ on vortex agitator, and 25w, shakes 20s under 1500rpm condition, shakes altogether 10 times.
7. described in claim 1,2,3 or 4, Nyctereutes procyonoides is being prepared the purposes in anaesthetic for Nyctereutes procyonoides with compound anesthetic.
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| US11998529B2 (en) | 2023-06-30 | 2024-06-04 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
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| US11806429B2 (en) | 2018-06-27 | 2023-11-07 | Bioxcel Therapeutics, Inc. | Film formulations containing dexmedetomidine and methods of producing them |
| US11890272B2 (en) | 2019-07-19 | 2024-02-06 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
| US11998528B1 (en) | 2023-03-23 | 2024-06-04 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
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